Title | Characterization of Plasmodium falciparum adenylyl cyclase-β and its role in erythrocytic stage parasites. |
Publication Type | Journal Article |
Year of Publication | 2012 |
Authors | Salazar E, Bank EM, Ramsey N, Hess KC, Deitsch KW, Levin LR, Buck J |
Journal | PLoS One |
Volume | 7 |
Issue | 6 |
Pagination | e39769 |
Date Published | 2012 |
ISSN | 1932-6203 |
Keywords | Adenylyl Cyclases, Animals, Base Sequence, DNA Primers, Erythrocytes, Humans, Plasmodium falciparum |
Abstract | The most severe form of human malaria is caused by the parasite Plasmodium falciparum. The second messenger cAMP has been shown to be important for the parasite's ability to infect the host's liver, but its role during parasite growth inside erythrocytes, the stage responsible for symptomatic malaria, is less clear. The P. falciparum genome encodes two adenylyl cyclases, the enzymes that synthesize cAMP, PfACα and PfACβ. We now show that one of these, PfACβ, plays an important role during the erythrocytic stage of the P. falciparum life cycle. Biochemical characterization of PfACβ revealed a marked pH dependence, and sensitivity to a number of small molecule inhibitors. These inhibitors kill parasites growing inside red blood cells. One particular inhibitor is selective for PfACβ relative to its human ortholog, soluble adenylyl cyclase (sAC); thus, PfACβ represents a potential target for development of safe and effective antimalarial therapeutics. |
DOI | 10.1371/journal.pone.0039769 |
Alternate Journal | PLoS ONE |
PubMed ID | 22761895 |
PubMed Central ID | PMC3383692 |
Grant List | T32 GM073546 / GM / NIGMS NIH HHS / United States R01 AI052390 / AI / NIAID NIH HHS / United States AI052390 / AI / NIAID NIH HHS / United States R01 AI064842 / AI / NIAID NIH HHS / United States R01 GM062328 / GM / NIGMS NIH HHS / United States AI064842 / AI / NIAID NIH HHS / United States T32 GM007739 / GM / NIGMS NIH HHS / United States |